The understanding of how gene expression is controlled is fundamental in elucidating the mechanisms involved in normal and abnormal cellular growth and differentiation. Recent developments indicate that a number of different regulatory circuits are operative in controlling individual bacterial operons and in integrating the products of these pathways into the general metabolism of the cell. These data suggest that these biosynthetic systems may be valuable models for discovering how gene expression is regulated in complex as well as simple organisms. With this in mind we wish to continue our study on the mechanisms involved in the control of the isoleucine-valine enzymes in E. coli and S. typhimurium. A variety of regulatory elements appear to be involved in this system including multivalent repression by multiple species of tRNA, structural gene proteins, rho factor, cyclic AMP and catabolite repression. We plan to examine these and other possible control components using in vivo and in vitro techniques in order to understand how these components interact at the molecular level to regulate gene expression.